6cug: Difference between revisions

Latest revision as of 15:11, 4 October 2023

Crystal structure of BC8B TCR-CD1b-PC complex

Structural highlights

6cug is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	CL, CUY, NAG, POV
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CD1B_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.^[1] ^[2]

Publication Abstract from PubMed

CD1 proteins are expressed on dendritic cells, where they display lipid antigens to T-cell receptors (TCRs). Here we describe T-cell autoreactivity towards ubiquitous human membrane phospholipids presented by CD1b. These T-cells discriminate between two major types of lipids, sphingolipids and phospholipids, but were broadly cross-reactive towards diverse phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine. The crystal structure of a representative TCR bound to CD1b-phosphatidylcholine provides a molecular mechanism for this promiscuous recognition. We observe a lateral escape channel in the TCR, which shunted phospholipid head groups sideways along the CD1b-TCR interface, without contacting the TCR. Instead the TCR recognition site involved the neck region phosphate that is common to all major self-phospholipids but absent in sphingolipids. Whereas prior studies have focused on foreign lipids or rare self-lipids, we define a new molecular mechanism of promiscuous recognition of common self-phospholipids including those that are known targets in human autoimmune disease.

A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids.,Shahine A, Reinink P, Reijneveld JF, Gras S, Holzheimer M, Cheng TY, Minnaard AJ, Altman JD, Lenz S, Prandi J, Kubler-Kielb J, Moody DB, Rossjohn J, Van Rhijn I Nat Commun. 2019 Jan 4;10(1):56. doi: 10.1038/s41467-018-07898-0. PMID:30610190^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shamshiev A, Donda A, Prigozy TI, Mori L, Chigorno V, Benedict CA, Kappos L, Sonnino S, Kronenberg M, De Libero G. The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity. 2000 Aug;13(2):255-64. PMID:10981968
↑ Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA, Modlin RL, Porcelli SA, Brinkmann V, Sugita M, Sandhoff K, Kaufmann SH, Schaible UE. Saposin C is required for lipid presentation by human CD1b. Nat Immunol. 2004 Feb;5(2):169-74. Epub 2004 Jan 11. PMID:14716313 doi:10.1038/ni1035
↑ Shahine A, Reinink P, Reijneveld JF, Gras S, Holzheimer M, Cheng TY, Minnaard AJ, Altman JD, Lenz S, Prandi J, Kubler-Kielb J, Moody DB, Rossjohn J, Van Rhijn I. A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids. Nat Commun. 2019 Jan 4;10(1):56. doi: 10.1038/s41467-018-07898-0. PMID:30610190 doi:https://dx.doi.org/10.1038/s41467-018-07898-0

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OCA

[1] Shamshiev A, Donda A, Prigozy TI, Mori L, Chigorno V, Benedict CA, Kappos L, Sonnino S, Kronenberg M, De Libero G. The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity. 2000 Aug;13(2):255-64. PMID:10981968

[2] Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA, Modlin RL, Porcelli SA, Brinkmann V, Sugita M, Sandhoff K, Kaufmann SH, Schaible UE. Saposin C is required for lipid presentation by human CD1b. Nat Immunol. 2004 Feb;5(2):169-74. Epub 2004 Jan 11. PMID:14716313 doi:10.1038/ni1035

[3] Shahine A, Reinink P, Reijneveld JF, Gras S, Holzheimer M, Cheng TY, Minnaard AJ, Altman JD, Lenz S, Prandi J, Kubler-Kielb J, Moody DB, Rossjohn J, Van Rhijn I. A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids. Nat Commun. 2019 Jan 4;10(1):56. doi: 10.1038/s41467-018-07898-0. PMID:30610190 doi:https://dx.doi.org/10.1038/s41467-018-07898-0

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==Crystal structure of BC8B TCR-CD1b-PC complex==
-<StructureSection load='6cug' size='340' side='right' caption='[[6cug]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='6cug' size='340' side='right'caption='[[6cug]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cug]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CUG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cug]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CUG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CUY:tetracosyl+octadecanoate'>CUY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6cug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cug OCA], [http://pdbe.org/6cug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cug RCSB], [http://www.ebi.ac.uk/pdbsum/6cug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cug ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CUY:tetracosyl+octadecanoate'>CUY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cug OCA], [https://pdbe.org/6cug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cug RCSB], [https://www.ebi.ac.uk/pdbsum/6cug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cug ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref>   Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/CD1B_HUMAN CD1B_HUMAN]] Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:10981968</ref> <ref>PMID:14716313</ref>  [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
+[https://www.uniprot.org/uniprot/CD1B_HUMAN CD1B_HUMAN] Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:10981968</ref> <ref>PMID:14716313</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 6cug" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
+*[[CD1|CD1]]
+*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Rossjohn, J]]
+[[Category: Homo sapiens]]
-[[Category: Shahine, A E]]
+[[Category: Large Structures]]
-[[Category: Antigen presenting molecule]]
+[[Category: Rossjohn J]]
-[[Category: Cd1b]]
+[[Category: Shahine AE]]
-[[Category: Immune system]]
-[[Category: Pc]]
-[[Category: Phosphatidylcholine]]
-[[Category: T cell receptor]]

6cug: Difference between revisions

Latest revision as of 15:11, 4 October 2023

Crystal structure of BC8B TCR-CD1b-PC complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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